The objective of the proposed study is to increase understanding of the factors that lead to severe corneal xerophthalmia in order to improve methods of prevention and treatment. No corneal xerophthalmia occurs unless the tissue is deprived of retinol but this deprivation can arise not only through lack of retinol in the diet but also through protein deficiency. This results in failure to synthesise retinol-binding protein (RBP) and pre-albumin (PA), and, without these proteins, retinol in not transported from the liver to the tissues in need. When malnutrition combines both protein and retinol deficiency, dosage with vitamin A may not be beneficial. I wish to study interrelations between the levels of protein and of retinol in the diet and the levels of RBP, PA and retinol in the blood and how these affect development of serious corneal xerophthalmia. Retinol-binding protein (RBP) and pre-albumin (PA) will be prepared from rat blood and antisera raised in rabbits. Immunodiffusion techniques will be used to determine the level of these proteins in the blood of rats made solely deficient in retinol, in protein or in both. The effect of dosage with retinol plamitate, in the above three groups of rats, and the effect of treatment on growth and eye signs of xerophthalmia will be recorded. There is an increase in collagenolytic enzymes in the cornea of the xerophthalmic rat, possibly derived from invading blood leucocytes. This may increase the danger of perforation. Corneal proteinases will be compared with those from neutrophils and their activity examined during development and healing of the corneal lesion. Corenal xerophthalmia will be studied in children in collaboration with Dr. G. Venkataswamy, Government Erskine Hospital, Madurai, who will take clinical responsibility. Retinol-binding protein, pre-albumin, retinol and retinol esters in blood will be estimated before and after treatment with retinol palmitate.